Elstein Deborah, Zimran Ari
b Gaucher Clinic, Shaare Zedek Medical Center, POB 3235, 12 Bayit Street, Jerusalem, 91031, Israel.
a Gaucher Clinic, Shaare Zedek Medical Center, POB 3235, 12 Bayit Street, Jerusalem, 91031, Israel.
Expert Rev Endocrinol Metab. 2013 Jul;8(4):333-339. doi: 10.1586/17446651.2013.811871.
Gaucher disease is a multisystem disorder caused by deficiency of β-glucocerebrosidase. Exogenously delivered enzyme replacement therapy (ERT) is currently standard of care. Since 1994, intravenously delivered recombinant ERT with imiglucerase (Cerezyme; Genzyme Corporation, Cambridge, MA, USA) improves hematological, visceral and skeletal features of Gaucher disease at dosages of 15-60 units/kg bodyweight/infusion, administered every other week (EOW). Velaglucerase alfa (VPRIV; Shire HGT, MA, USA) is a human wild-type-sequenced ERT produced in human cell lines using proprietary Gene-Activation technology (Shire HGT). This article describes the results of a Phase I/II seminal trial in treatment-naive non-neuronopathic patients (including stepwise dose reduction to 30 units/kg/EOW) and three Phase III trials (two doses: 45 or 60 units/kg/EOW; switch-over from imiglucerase at identical dose; head-to-head with imiglucerase, 60 units/kg/EOW) and Phase III extension trial. Velaglucerase alfa was approved in 2010 in many countries; based on clinical trial experience, it is safe and effective in treatment-naive and switch-over patients, children and adults, splenectomized patients and those with an intact spleen.
戈谢病是一种由β-葡萄糖脑苷脂酶缺乏引起的多系统疾病。目前，外源性酶替代疗法（ERT）是标准治疗方法。自1994年以来，静脉注射重组ERT药物伊米苷酶（思而赞；美国马萨诸塞州剑桥市健赞公司），每两周一次（EOW），以15 - 60单位/千克体重/次的剂量给药，可改善戈谢病的血液学、内脏和骨骼症状。维拉苷酶α（VPRIV；美国马萨诸塞州夏尔HGT公司）是一种利用专利基因激活技术（夏尔HGT）在人细胞系中生产的人野生型序列ERT。本文介绍了一项针对未接受过治疗的非神经病变患者的I/II期开创性试验（包括逐步将剂量降至30单位/千克/EOW）、三项III期试验（两种剂量：45或60单位/千克/EOW；从相同剂量的伊米苷酶转换；与60单位/千克/EOW的伊米苷酶进行头对头比较）以及III期扩展试验的结果。维拉苷酶α于2010年在许多国家获得批准；基于临床试验经验，它在未接受过治疗的患者、转换患者、儿童和成人、脾切除患者以及脾脏完整的患者中都是安全有效的。
